Immunoglobulin GM and KM allotypes and vaccine immunity

Immunoglobulin (Ig) GM and KM allotypes are genetic markers of gamma and kappa-type light chains, respectively. The striking qualitative and quantitative differences in the distribution of these determinants among different races raise questions concerning the nature of the evolutionary selective mechanism that maintains this variation. Associations between Ig allotypes and specific antibody responses could be a selective force for the maintenance of various haplotypes and their frequencies. Data from several studies reporting significant associations between certain GM and KM allotypes and immune responsiveness to polysaccharide vaccines and to particular infectious pathogens support this hypothesis. Possible ways in which constant (C)-region allotypes could contribute to the antibody specificity include the following: (i) certain alleles coding for allotypes may be in linkage disequilibrium with particular variable (V)-region determinants associated with immune responsiveness; (ii) they could directly contribute to the formation of specific idiotypes, as shown for the T15 system in mice; and (iii) allotype-associated structural variability in the C-region could modulate the kinetic competence of the antigen binding sites.